Efficacy of Tocilizumab in Limbic Encephalitis with Anti-CASPR2 Antibodies.

We report the case of a 64-year-old man who presented with subacute memory, balance impairment, behavioral and mood changes, and epileptic seizures. Magnetic resonance imaging (MRI) showed bilateral hippocampal abnormalities. Brain [18F]-FDG fluorodeoxyglucose positron emission tomography (PET) revealed hypometabolism in both the temporal lobe as well as in the left insular and parietal regions. The clinical and neuroradiological picture and the detection of anti-CASPR2 antibodies in serum oriented the diagnosis towards autoimmune limbic encephalitis. Intravenous high-dose steroid and immunoglobulin treatments were ineffective. We did not use rituximab for the presence of antibodies to HbcAg positivity. Tocilizumab given intravenously 8 mg/kg once a month for six months and then subcutaneously 162 mg every week for six months resulted in clinical and neuroradiological improvement. These data support the efficacy of tocilizumab in autoimmune limbic encephalitis associated with anti-CASPR2 antibodies, which has been sporadically reported in the literature.

The novel PSEN1 M84V mutation associated to frontal dysexecutive syndrome, spastic paraparesis, and cerebellar atrophy in a dominant Alzheimer's disease family.

We identified the novel PSEN1 pathogenic mutation M84V in 3 patients belonging to a large kindred affected by autosomal dominant Alzheimer's disease (AD). The clinical phenotype was characterized by early onset dementia in 14 affected subjects over 3 generations. Detailed clinical, imaging and genetic assessment was performed. We highlighted the presence of unusual symptoms such as frontal executive syndrome, psychosis and spastic paraparesis in these patients. Spastic paraparesis has been reported in other PSEN1 mutations in adjacent codons, suggesting that the position of the genetic defect may affect the clinical expression, although this phenotype can occur in mutations throughout the whole PSEN1 gene. Brain magnetic resonance imaging showed diffuse cortical atrophy, but also atrophy of cerebellar lobules, mainly involving Crus I, in 2 patients without cerebellar motor deficits. These neuroimaging results were consistent with recent findings about the association between sporadic AD and distinct and circumscribed cerebellar atrophy. The present work acknowledged the novel PSEN1 pathogenic mutation M84V and might contribute to the ongoing debate about the involvement of cerebellum in AD.

Behavioral and psychological symptoms in Alzheimer's disease: frequency and relationship with duration and severity of the disease.

The occurrence of behavioral and psychological symptoms of dementia (BPSD) is currently recognized as an important aspect of Alzheimer's disease (AD). We evaluated the frequency and severity of BPSD with the Neuropsychiatric Inventory across the various degrees and phases of the disease in 50 consecutive AD outpatients. Apathy, aberrant motor activity, dysphoria and anxiety were the symptoms most frequently reported by the caregivers, ranging in the whole study sample from 46 to 74%. A clear trend towards increasing frequency with the severity of disease was found for delusions, hallucinations and aberrant motor activity. A major effect of the duration of the disease was found in the probability of developing hallucinations and aberrant motor activity. Apart from hallucinations, all BPSD were present starting from a mild degree of dementia. A better understanding of the global spectrum of BPSD in AD is warranted in order to improve the allocation of health resources toward the treatment of dementia.